3VKJ

Crystal structure of Sulfolobus shibatae isopentenyl diphosphate isomerase, octameric form

Summary for 3VKJ

• Entry DOI: 10.2210/pdb3vkj/pdb
• Descriptor: Isopentenyl-diphosphate delta-isomerase, 1-DEOXY-1-(7,8-DIMETHYL-2,4-DIOXO-3,4-DIHYDRO-2H-BENZO[G]PTERIDIN-1-ID-10(5H)-YL)-5-O-PHOSPHONATO-D-RIBITOL (3 entities in total)
• Functional Keywords: type 2 isopentenyl diphosphate isomerase, isomerase
• Biological source: Sulfolobus shibatae
• Cellular location: Cytoplasm (By similarity): P61615
• Total number of polymer chains: 4
• Total formula weight: 163736.70

Authors

Nakatani, H.,Goda, S.,Unno, H.,Nagai, T.,Yoshimura, T.,Hemmi, H. (deposition date: 2011-11-17, release date: 2012-05-30, Last modification date: 2024-03-20)

Primary citation

Nakatani, H.,Goda, S.,Unno, H.,Nagai, T.,Yoshimura, T.,Hemmi, H.
Substrate-Induced Change in the Quaternary Structure of Type 2 Isopentenyl Diphosphate Isomerase from Sulfolobus shibatae.
J.Bacteriol., 194:3216-3224, 2012

PubMed Abstract: Type 2 isopentenyl diphosphate isomerase catalyzes the interconversion between two active units for isoprenoid biosynthesis, i.e., isopentenyl diphosphate and dimethylallyl diphosphate, in almost all archaea and in some bacteria, including human pathogens. The enzyme is a good target for discovery of antibiotics because it is essential for the organisms that use only the mevalonate pathway to produce the active isoprene units and because humans possess a nonhomologous isozyme, type 1 isopentenyl diphosphate isomerase. However, type 2 enzymes were reportedly inhibited by mechanism-based drugs for the type 1 enzyme due to their surprisingly similar reaction mechanisms. Thus, a different approach is now required to develop new inhibitors specific to the type 2 enzyme. X-ray crystallography and gel filtration chromatography revealed that the enzyme from a thermoacidophilic archaeon, Sulfolobus shibatae, is in the octameric state at a high concentration. Interestingly, a part of the regions that are involved in the substrate binding in the previously reported tetrameric structures is integral to the formation of the tetramer-tetramer interface in the substrate-free octameric structure. Site-directed mutagenesis at such regions resulted in stabilization of the tetramer. Small-angle X-ray scattering, tryptophan fluorescence, and dynamic light scattering analyses showed that substrate binding causes the dissociation of an octamer into tetramers. This property, i.e., incompatibility between octamer formation and substrate binding, might provide clues to develop new specific inhibitors of the archaeal enzyme.

PubMed: 22505674
DOI: 10.1128/JB.00068-12

Experimental method

X-RAY DIFFRACTION (1.7 Å)